Xu Yinfeng, Wan Wei, Shou Xin, Huang Rui, You Zhiyuan, Shou Yanhong, Wang Lingling, Zhou Tianhua, Liu Wei
a Department of Biochemistry and Molecular Biology , Program in Molecular and Cell Biology, Zhejiang University School of Medicine , Hangzhou , China.
b Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou , China.
Autophagy. 2016 Jul 2;12(7):1118-28. doi: 10.1080/15548627.2016.1175693. Epub 2016 May 12.
Cells control their metabolism through modulating the anabolic and catabolic pathways. TP53INP2/DOR (tumor protein p53 inducible nuclear protein 2), participates in cell catabolism by serving as a promoter of autophagy. Here we uncover a novel function of TP53INP2 in protein synthesis, a major biosynthetic and energy-consuming anabolic process. TP53INP2 localizes to the nucleolus through its nucleolar localization signal (NoLS) located at the C-terminal domain. Chromatin immunoprecipitation (ChIP) assays detected an association of TP53INP2 with the ribosomal DNA (rDNA), when exclusion of TP53INP2 from the nucleolus repressed rDNA promoter activity and the production of ribosomal RNA (rRNA) and proteins. The removal of TP53INP2 also impaired the association of the POLR1/RNA polymerase I preinitiation complex (PIC) with rDNA. Further, TP53INP2 interacts directly with POLR1 PIC, and is required for the assembly of the complex. These data indicate that TP53INP2 promotes ribosome biogenesis through facilitating rRNA synthesis at the nucleolus, suggesting a dual role of TP53INP2 in cell metabolism, assisting anabolism on the nucleolus, and stimulating catabolism off the nucleolus.
细胞通过调节合成代谢和分解代谢途径来控制其新陈代谢。TP53INP2/DOR（肿瘤蛋白p53诱导核蛋白2）作为自噬的促进因子参与细胞分解代谢。在此，我们发现了TP53INP2在蛋白质合成中的新功能，蛋白质合成是一个主要的生物合成和耗能的合成代谢过程。TP53INP2通过其位于C末端结构域的核仁定位信号（NoLS）定位于核仁。染色质免疫沉淀（ChIP）分析检测到TP53INP2与核糖体DNA（rDNA）相关联，当TP53INP2从核仁中排除时，rDNA启动子活性以及核糖体RNA（rRNA）和蛋白质的产生受到抑制。去除TP53INP2也损害了POLR1/RNA聚合酶I预起始复合物（PIC）与rDNA的结合。此外，TP53INP2直接与POLR1 PIC相互作用，并且是该复合物组装所必需的。这些数据表明，TP53INP2通过促进核仁处的rRNA合成来促进核糖体生物发生，这表明TP53INP2在细胞代谢中具有双重作用，在核仁上协助合成代谢，并在核仁外刺激分解代谢。
